Using PSMA (prostate-specific membrane antigen) evaluation on prostate biopsies for risk stratification at time of initial diagnosis.

6 Background: Stratifying prostate cancer (PCa) patients into risk groups at time of initial diagnosis for individual treatment decision is still a major clinical challenge. PSMA expression has emerged as a promising prognostic biomarker since its overexpression in radical prostatectomy specimens (RP) has been linked to disease recurrence. Aim of our study was to assess the prognostic value of PSMA on prostate biopsies (Bx) thus improving risk stratification at time of initial diagnosis. Methods: Immunohistochemistry for PSMA expression was performed on 294 Bx with corresponding RP, 621 primary tumor foci from 242 RP, 43 locally advanced or recurrent tumors, 34 lymph node metastases, 78 distant metastases, and 52 benign prostatic samples. Grade group, PSA, TNM-, and R-status were assessed as clinico-pathologic features. Primary endpoint was recurrence-free survival (RFS). Chi-square, ANOVA-analyses, Cox regression and log rank tests were performed for statistical analyses. Results: PSMA expression significantly associates with grade group and initial PSA level. Elevated PSMA expression on both RP and Bx significantly correlates with an increased risk of disease recurrence after curative surgery. 5-year RFS rates are 88.2%, 74.2%, 67.7%, and 26.8% for patients with no, low, medium, or high PSMA expression on Bx, respectively. Elevated PSMA level on Bx predict a 4-fold increased risk of disease recurrence independently from initial PSA and grade group on Bx. PSMA expression significantly increases during PCa progression. Conclusions: PSMA qualifies as an independent prognostic biomarker on Bx at time of initial diagnosis in addition to the established markers PSA and grade group. PSMA predicts disease recurrence following curative surgery and potentially improves the discrimination indolent vs. aggressive disease. We propose the routine assessment of PSMA expression on Bx for outcome prediction and risk stratification at time of initial diagnosis prior to treatment decision.

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Increased expression of senescence markers p14ARFand p16INK4ain breast cancer is associated with an increased risk of disease recurrence and poor survival outcome

Histopathology ◽

10.1111/his.12948 ◽

2016 ◽

Vol 69 (3) ◽

pp. 479-491 ◽

Cited By ~ 10

Author(s):

Rahmawati Pare ◽

Joo-Shik Shin ◽

Cheok Soon Lee

Keyword(s):

Breast Cancer ◽

Disease Recurrence ◽

Survival Outcome ◽

Poor Survival ◽

Increased Risk ◽

Poor Survival Outcome ◽

Risk Of Disease

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Impact of dose-capping chemotherapy in concurrent chemoradiotherapy in rectal cancer patients

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155220962192 ◽

2020 ◽

pp. 107815522096219

Author(s):

Ran Yang ◽

Moftah Younis ◽

Kurian Joseph ◽

Sunita Ghosh ◽

Tirath Nijjar ◽

...

Keyword(s):

Rectal Cancer ◽

Cancer Patients ◽

Binary Logistic Regression ◽

Disease Recurrence ◽

Kaplan Meier ◽

Significant Toxicity ◽

Increased Risk ◽

Risk Of Disease ◽

Chemotherapy Dose

Introduction The study evaluated the effect of chemotherapy dose-capping on disease recurrence, toxicity and survival of rectal cancer patients treated with chemoradiotherapy (CRT). Methods 601 consecutive rectal cancer patients treated with concurrent CRT were retrospectively analysed. Dose-capped patients were defined as having a body surface area (BSA) ≥2.0 m2 and who received <95% full weight-based chemotherapy dose. Binary logistic regression was used to study the factors associated with the outcome variables (capped vs. uncapped). Kaplan-Meier estimation evaluated significant predictors of survival. Results The median follow-up time was 7.54 years. The rate of disease recurrence was significantly higher in dose-capped patients (35%) compared to those without dose-capping (24%, P = 0.016). The adjusted odds ratio for dose-capped patients experiencing recurrence was 1.64 compared to uncapped patients (95% CI, 1.10–2.43). Overall, dose-capped patients were less likely to experience significant toxicity requiring dose reduction and/or treatment break when compared to uncapped patients (15% and 28% respectively, P = 0.008).There was significant differences in PFS between capped and uncapped group (77% vs. 85%; P = 0.017). The 5-year OS in the capped group was 75.0%, and 80% in the uncapped group ( P = 0.149). Conclusions Rectal cancer patients treated with dose-capped CRT were at increased risk of disease recurrence. Patients dosed by actual BSA did experience excessive toxicity compared to dose-capped group. We recommend that chemotherapy dose-capping based on BSA should not be practiced in rectal cancer patients undergoing CRT.

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Delay in radiotherapy is associated with an increased risk of disease recurrence in women with ductal carcinoma in situ

Cancer ◽

10.1002/cncr.30972 ◽

2017 ◽

Vol 124 (1) ◽

pp. 46-54 ◽

Cited By ~ 21

Author(s):

Elizabeth Shurell ◽

Cristina Olcese ◽

Sujata Patil ◽

Beryl McCormick ◽

Kimberly J. Van Zee ◽

...

Keyword(s):

Ductal Carcinoma In Situ ◽

Carcinoma In Situ ◽

Ductal Carcinoma ◽

Disease Recurrence ◽

Increased Risk ◽

Risk Of Disease

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STAT3 regulated ARF expression suppresses prostate cancer metastasis

Nature Communications ◽

10.1038/ncomms8736 ◽

2015 ◽

Vol 6 (1) ◽

Cited By ~ 78

Author(s):

Jan Pencik ◽

Michaela Schlederer ◽

Wolfgang Gruber ◽

Christine Unger ◽

Steven M. Walker ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Progression ◽

Cancer Metastasis ◽

Prognostic Markers ◽

Disease Recurrence ◽

Therapeutic Benefit ◽

Increased Risk ◽

Prostate Cancer Metastasis ◽

Risk Of Disease ◽

Stat3 Signalling

Abstract Prostate cancer (PCa) is the most prevalent cancer in men. Hyperactive STAT3 is thought to be oncogenic in PCa. However, targeting of the IL-6/STAT3 axis in PCa patients has failed to provide therapeutic benefit. Here we show that genetic inactivation of Stat3 or IL-6 signalling in a Pten-deficient PCa mouse model accelerates cancer progression leading to metastasis. Mechanistically, we identify p19ARF as a direct Stat3 target. Loss of Stat3 signalling disrupts the ARF–Mdm2–p53 tumour suppressor axis bypassing senescence. Strikingly, we also identify STAT3 and CDKN2A mutations in primary human PCa. STAT3 and CDKN2A deletions co-occurred with high frequency in PCa metastases. In accordance, loss of STAT3 and p14ARF expression in patient tumours correlates with increased risk of disease recurrence and metastatic PCa. Thus, STAT3 and ARF may be prognostic markers to stratify high from low risk PCa patients. Our findings challenge the current discussion on therapeutic benefit or risk of IL-6/STAT3 inhibition.

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SUN-119 Identification of Novel Mirnas Found to Be Differentially Expressed Between ATA Risk Stratification Groups in Papillary Thyroid Carcinoma

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.578 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Luisa Fernanda Olaya A ◽

Joanne Malek ◽

Brodie Hookins ◽

Tripti Joshi ◽

Watson Zara ◽

...

Keyword(s):

Risk Stratification ◽

Cancer Progression ◽

Normal Tissue ◽

Disease Recurrence ◽

Differentially Expressed ◽

Roc Curve Analysis ◽

Intermediate Group ◽

Qrt Pcr ◽

Tiered System ◽

Risk Of Disease

Abstract The study of miRNAs in PTC has shown that these molecules can help in the diagnosis, prognosis and also as therapeutic candidates [1]. miRNAs are known to be differentially expressed in PTC compared to non-cancerous tissue and a few studies have shown association with some clinico-pathological features. However, little is known regarding their expression in relation to risk of disease progression. In this study, we examined the expression of miRNAs in patients diagnosed with PTC in association with risk of disease recurrence and/or persistence. Patients were classified by three endocrinologists to either high (H) or low (L) risk according to ATA Risk Stratification. PTC tissue was micro-dissected from Formalin Fixed Paraffin Embedded (FFPE) tissue for analysis. OPenArray analysis showed that 21 miRNAs were differentially expressed in H-L groups (n=4/grp). qRT-PCR was used to confirm these differences in a larger cohort of PTC (H=46; L=58). This comparison also included comparisons between cancer and normal tissue and investigation of miRNAs known to be differentially expressed (i.e miRNAs 222, 221 and 146b). All analysis was performed in Rstudio using ΔΔCt relative to expression of miR-16 which was not altered by PTC. By qRT-PCR, only 3 of the 21 miRNAs identified by OpenArray analysis, were differentially expressed in H vs L risk (each P<0.05). These miRNAs are known to be involved in cancer progression pathways but have not been reported in PTC. Individual Receiver Operating Characteristic (ROC) curve analysis of these 3 miRNAs had AUC as follows (miR 1: 0.62, miR 2: 0.62, miR 3: 0.64,) and when analyzed together, the AUC model was improved (AUC=0.76). Examination of cancer vs normal tissue confirmed higher expression miR-146b, miR-221 and miR-222 (each P<0.05). However, these miRNAs were not differentially expressed when H vs L risk were analysed. In this study, we identified 3 miRNAs with potential utility for the stratification of patients into those with H or L risk disease recurrence/persistence. As the current ATA 3-tiered system used is still a reflection of the continuum of risk that patients have, whether these 3 miRNAs may have the utility to further stratify those in the intermediate group remains to be investigated. Reference: 1. Ramírez-Moya, J. and P. Santisteban, miRNA-Directed Regulation of the Main Signaling Pathways in Thyroid Cancer. Frontiers in Endocrinology, 2019. 10: p. 430.

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Serum metabolomic profiles identify ER-positive early breast cancer patients at increased risk of disease recurrence in a multicentre population

Annals of Oncology ◽

10.1093/annonc/mdw364.09 ◽

2016 ◽

Vol 27 ◽

pp. vi45

Author(s):

C.D. Hart ◽

A. Vignoli ◽

L. Tenori ◽

L. Biganzoli ◽

E. Risi ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Early Breast Cancer ◽

Disease Recurrence ◽

Breast Cancer Patients ◽

Increased Risk ◽

Er Positive ◽

Risk Of Disease

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471 MGMT Methylation As a Novel Biomarker for the Identification of Stage III Colorectal Cancers At High-Risk of Disease Recurrence Following Curative Surgery

Gastroenterology ◽

10.1016/s0016-5085(13)60315-7 ◽

2013 ◽

Vol 144 (5) ◽

pp. S-85 ◽

Cited By ~ 1

Author(s):

Yoshiko Mori ◽

Takeshi Nagasaka ◽

Hiroshi Tazawa ◽

Yuzo Umeda ◽

Tatsuya Morikawa ◽

...

Keyword(s):

High Risk ◽

Disease Recurrence ◽

Stage Iii ◽

Colorectal Cancers ◽

Mgmt Methylation ◽

Curative Surgery ◽

Risk Of Disease

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EPEN-36. THE TREATMENT OUTCOME OF PAEDIATRIC SUPRATENTORIAL C11ORF95-RELA FUSED EPENDYMOMA: A COMBINED REPORT FROM E-HIT SERIES AND AUSTRALIAN NEW ZEALAND CHILDREN’S HAEMATOLOGY/ONCOLOGY GROUP

Neuro-Oncology ◽

10.1093/neuonc/noaa222.171 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii315-iii315

Author(s):

Chia Huan Ng ◽

Denise Obrecht ◽

Molly Buntine ◽

Olivia Wells ◽

Martin A Campbell ◽

...

Keyword(s):

Risk Stratification ◽

Surgical Resection ◽

Molecular Analysis ◽

Treatment Decision ◽

Progression Free Survival ◽

Molecular Classification ◽

Disease Recurrence ◽

Outcome Data ◽

Treatment Decision Making ◽

Supratentorial Ependymoma

Abstract AIM Advances in molecular classification of paediatric ependymoma have been pivotal in improving risk stratification and understanding of this disease. C11orf95-RELA fused supratentorial ependymoma (ST-EPN) have been reported to have a poor outcome, with 10-year overall survival (OS) of 49% and progression free survival (PFS) of 19%. A cohort of patients from multiple international institutions with molecularly confirmed C11orf95-RELA fused ST-EPN were reviewed to assess their disease behaviour. METHOD: We reviewed patients with molecularly determined C11orf95-RELA supratentorial ependymoma diagnosed between 1999 – 2019. Demographic information, extent of surgical resection, use of radiotherapy and/or chemotherapy, disease recurrence, treatment at recurrence and clinical outcome data was collected. PFS and OS of all patients were estimated using Kaplan-Meier method. RESULTS A total of 76 ST-EPN patients with C11orf95-RELA fusion were identified (median age: 7 years3 months, range: 5 months – 18 years7 months). 58 patients (76.3%) had complete surgical resection. 70 patients(92.1%) received radiotherapy. 55 patients(72.3%) received chemotherapy. The 10-year OS of C11orf95-RELA fused ST-EPN was 72.4% and PFS was 63.8%. In contrast, ST-EPN at a single institution with unconfirmed molecular status had an OS of 61.1% and PFS of 34.9%. CONCLUSION Detailed molecular analysis identified distinct subgroups of patients with ST-EPN. Patients from this cohort with C11orf95-RELA methylation profiles had a significantly higher OS compared to previous reports and those with unconfirmed fusion status, emphasising the critical importance of complete molecular profiling to assist in treatment decision making. Complete molecular analysis in future prospective cohorts is essential for accurate risk stratification and treatment selection.

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